Molecular Interface of Neuronal Innate Immunity, Synaptic Vesicle Stabilization, and Presynaptic Homeostatic Plasticity.
Molecular Interface of Neuronal Innate Immunity, Synaptic Vesicle Stabilization, and Presynaptic Homeostatic Plasticity.
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DOI：
10.1016/j.neuron.2018.09.048
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发表时间：
2018-12-05
期刊：
影响因子：
16.2
通讯作者：
Davis GW
中科院分区：
文献类型：
--
作者：
Harris N;Fetter RD;Brasier DJ;Tong A;Davis GW
我们定义了神经元内先天免疫信号的稳态功能。对先天免疫信号基因IMD、IKKβ、Tak1和Relish的遗传分析表明，每个基因对突触前稳态可塑性（PHP）都是必不可少的。随后的分析定义了PHP的快速诱导（发生在几秒钟内）如何与PHP的终身维持相协调，这是一个从无脊椎动物到哺乳动物的时间过程。我们定义了一个新的突触前先天免疫信号的分歧。Tak1（Map3K）在局部起作用，并对快速PHP诱导有选择性。IMD、IKKβ和Relish对于PHP的长期维护至关重要。然后，我们定义如何Tak1控制囊泡释放。Tak1稳定停靠的囊泡状态，这对于易释放囊泡池的稳态扩张是必不可少的。这代表了一种控制囊泡释放的机制，以及先天免疫信号传导与囊泡融合装置和稳态可塑性的界面。Harris等人，证明神经元先天免疫信号协调突触前稳态可塑性的快速诱导和持续表达。信号传导包括Map3K Tak1，其通过稳定对接的突触囊泡状态直接与囊泡释放机制介导。
We define a homeostatic function for innate immune signaling within neurons. A genetic analysis of the innate immune signaling genes IMD, IKKβ, Tak1 and Relish demonstrates that each is essential for presynaptic homeostatic plasticity (PHP). Subsequent analyses define how the rapid induction of PHP (occurring in seconds) can be coordinated with the life-long maintenance of PHP, a time course that is conserved from invertebrates to mammals. We define a novel bifurcation of presynaptic innate immune signaling. Tak1 (Map3K) acts locally and is selective for rapid PHP induction. IMD, IKKβ and Relish are essential for long-term PHP maintenance. We then define how Tak1 controls vesicle release. Tak1 stabilizes the docked vesicle state, which is essential for the homeostatic expansion of the readily releasable vesicle pool. This represents a mechanism for the control of vesicle release, and an interface of innate immune signaling with the vesicle fusion apparatus and homeostatic plasticity. Harris et al., demonstrate that neuronal innate immune signaling coordinates the rapid induction and sustained expression of presynaptic homeostatic plasticity. Signaling includes the Map3K Tak1, which directly interfaces with the vesicle release machinery by stabilizing the docked synaptic vesicle state.
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